NEOPLASIA DR.ROOPAPathophysiology Premed 2

Neoplasia Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasm is an abnormal mass of tissue as a result of neoplasia. Uncontrollable or abnormal proliferation of cells. Uncontrollable or abnormal proliferation of cells.

Types Types A neoplasm can be benign, potentially malignant (pre-cancer), or malignant (cancer). A neoplasm can be benign, potentially malignant (pre-cancer), or malignant (cancer).benignpre-cancercancerbenignpre-cancercancer Benign neoplasms include uterine fibroids and melanocytic nevi (skin moles). They do not transform into cancer. Benign neoplasms include uterine fibroids and melanocytic nevi (skin moles). They do not transform into cancer.uterine fibroidsmelanocytic nevicanceruterine fibroidsmelanocytic nevicancer

Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but, given enough time, will transform into a cancer. Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but, given enough time, will transform into a cancer. carcinoma in situcancer carcinoma in situcancer

Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host. Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host. cancermetastases cancermetastases

Metastasis sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part. Metastasis sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part.diseaseorgandiseaseorgan cancer cells can break away, leak, or spill from a primary tumor, enter lymphatic and blood vessels, circulate through the bloodstream, and be deposited within normal tissue elsewhere in the body. cancer cells can break away, leak, or spill from a primary tumor, enter lymphatic and blood vessels, circulate through the bloodstream, and be deposited within normal tissue elsewhere in the body. cancer cellsprimary tumorlymphatic blood vessels bloodstreamtissue cancer cellsprimary tumorlymphatic blood vessels bloodstreamtissue

Malignant vs Benign (+) invasion: spread to nearby structures (+) invasion: spread to nearby structures (+)metastasis: spread to distant structures (+)metastasis: spread to distant structures (+)anaplasia : (+)anaplasia : cells are very different from the normal cells cells are very different from the normal cells (poorly differentiated) (-) invasion (-) invasion (+) capsule (+) capsule (-)metastasis (-)metastasis Resemble the tissue of origin (well differentiated) Resemble the tissue of origin (well differentiated)

Anaplasia Pleomorphism Pleomorphism Hyperchromatism (dark nuclei) Hyperchromatism (dark nuclei) Increased nuclear-cytoplasm ratio Increased nuclear-cytoplasm ratio Abnormal mitosis Abnormal mitosis Prominent nucleoli Prominent nucleoli The more anaplastic, the more aggressive the cancer The more anaplastic, the more aggressive the cancer The more anaplastic, the more responsive to chemo and radiotherapy The more anaplastic, the more responsive to chemo and radiotherapy

Forms of Malignant tumors Carcinoma: malignant tumor of epithelial origin Carcinoma: malignant tumor of epithelial origin 1. squamous cell carcinoma cancer of the skin cancer of the esophagus 2. adenocarcinoma: glands cancer of the breast cancer of the pancreas 3. transitional cell carcinoma cancer of the bladder

Forms of Malignant tumors Sarcoma: of mesenchymal origin Sarcoma: of mesenchymal originosteosarcomarhabdosarcomaleiomyosarcomaliposarcoma Teratoma: from all 3 germ layers Teratoma: from all 3 germ layers skin, bone, cartilage, teeth, intestinal ovaries and testis: most common may also be benign

Osteosarcoma

Liposarcoma

Teratoma

Forms of Benign tumors Papilloma: Adenoma: glandular epithelium Papilloma: Adenoma: glandular epithelium -ovary, breast Mesenchymal origin Mesenchymal origin -leiomyoma, lipoma, fibroma, chondroma

Papilloma epithelium of skin, larynx and tongue; fingerlike projections

Properties of Neoplasms Monoclonality Monoclonality the neoplasm comes from a single precursor cell Invasion Invasion enters the blood vessels and lymphatics Metastases Metastases blood vessels: sarcomas lymphatic: carcinoma

Properties of Neoplasms Common sites of metastases Common sites of metastases liver, lung, brain, adrenal glands, lymph nodes bone marrow.

Clinical signs of malignancy Cachexia Cachexia wasting, weakness, weight loss, anemia, infection cause: CACHECTIN Endocrine abnormalities Endocrine abnormalitiesprolactinoma ovarian tumors Paraneoplastic syndromes Paraneoplastic syndromes ectopic production of hormones lung cancer : ACTH

Carcinogenesis and carcinogens Chemical agents Chemical agents Physical agents Physical agents Viruses Viruses Activation of cancer-promoting genes Activation of cancer-promoting genes Inhibition of cancer-suppressing genes Inhibition of cancer-suppressing genes

Carcinogenesis and carcinogens Cigarette smoking : lung CA, laryngeal CA Cigarette smoking : lung CA, laryngeal CA Excessive sun: Skin CA Excessive sun: Skin CA Asbestos: Mesothelioma Asbestos: Mesothelioma Nitrosamines: Gastric CA Nitrosamines: Gastric CA Alcohol: Esophageal CA Alcohol: Esophageal CA Low-fiber diet: Colon CA Low-fiber diet: Colon CA

Carcinogenesis and carcinogens High-fat diet: Breast CA High-fat diet: Breast CA Aniline dyes: bladder Ca Aniline dyes: bladder Ca Aflatoxin: liver CA Aflatoxin: liver CA PVC: Angiosarcoma of the liver PVC: Angiosarcoma of the liver DES: Clear cell adenocarcinoma of the vagina DES: Clear cell adenocarcinoma of the vagina Nickle, chromium, uranium: lung CA Nickle, chromium, uranium: lung CA

Carcinogenesis and carcinogens HTLV – 1: Adult T cell leukemia HTLV – 1: Adult T cell leukemia HPV: cervical CA HPV: cervical CA EBV: Nasopharyngeal CA, Burkitts lymphoma EBV: Nasopharyngeal CA, Burkitts lymphoma HBV: Hepatocellular CA HBV: Hepatocellular CA HHV-8: Kaposi sarcoma HHV-8: Kaposi sarcoma Helicobacter pylori: Gastric CA Helicobacter pylori: Gastric CA

An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a tumor cell. An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a tumor cell.gene mutatedtumorgene mutatedtumor Oncogenes Oncogenes bcl-2: inhibits apoptosis Follicular lymphoma Follicular lymphoma c-myc : Burkitts lymphoma c-myc : Burkitts lymphoma

Cancer suppresor genes (anti oncogene) A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.genecellmutatedgenecellmutated p53: “ guardian of the genome” p53: “ guardian of the genome” mutated in 50% of all malignant tumors mutated in 50% of all malignant tumors causes cell cycle arrest in G1, time for DNA repair causes cell cycle arrest in G1, time for DNA repair unsuccessful repair: apoptosis unsuccessful repair: apoptosis

LI-FRAUMENI SYNDROME LI-FRAUMENI SYNDROME familial cancers of the breast, soft tissue sarcomas, brain tumors, leukemias.

Cancer suppresor genes (anti oncogene) WT-1 and WT-2: Wilms tumor WT-1 and WT-2: Wilms tumor BRCA -1: breast and ovarian CA BRCA -1: breast and ovarian CA BRCA – 2: breast CA BRCA – 2: breast CA

The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. cancer

Grading: degree of differentiation of the cells Grading: degree of differentiation of the cells Staging: spread of the tumor Staging: spread of the tumor -uses the TNM system TNM staging system TNM staging system TNM staging system TNM staging system Cancer staging can be divided into a clinical stage and a pathologic stage. In the TNM (Tumor, Node, Metastasis) Cancer staging can be divided into a clinical stage and a pathologic stage. In the TNM (Tumor, Node, Metastasis)TNM

system, clinical stage and pathologic stage are denoted by a small "c" or "p" before the stage. system, clinical stage and pathologic stage are denoted by a small "c" or "p" before the stage.

CANCER TREATMENT CANCER TREATMENT CHEMOTHERAP Y CHEMOTHERAP Y CYTOTOXIC DRUGS+BODY DEFENSES CYTOTOXIC DRUGS+BODY DEFENSES SINGLE AGENT SINGLE AGENT COMBINATION CHEMOTHERAPY COMBINATION CHEMOTHERAPY _AVOIDS SINGLE AGENT RESISTANCE _AVOIDS SINGLE AGENT RESISTANCE CAN USE LOWER DOSE CAN USE LOWER DOSE BETTER REMISSION AND CURE RATE BETTER REMISSION AND CURE RATE RADIATION RADIATION TARGETS DNA TARGETS DNA KILL TUMOR WITHOUT DAMAGE TO SURROUNDING TISSUES KILL TUMOR WITHOUT DAMAGE TO SURROUNDING TISSUES TUMOR MUST BE ACCESSIBLE TUMOR MUST BE ACCESSIBLE

SURGERY SURGERY METHOD OF CHOICE,CAN REMOVE ENTIRE TUMOR,DEBULKING METHOD OF CHOICE,CAN REMOVE ENTIRE TUMOR,DEBULKING ADJUVANT CHEMOTHERAPY OR RADIATION ADJUVANT CHEMOTHERAPY OR RADIATION IMMUNOTHERAPY IMMUNOTHERAPY.ELIMINATES CANCER CELLS ONLY.ELIMINATES CANCER CELLS ONLY.PROVIDES PROTECTION AGAINST RECURRENCE.PROVIDES PROTECTION AGAINST RECURRENCE.T_CELL BASED OR ANTIBODY RESPONSES.T_CELL BASED OR ANTIBODY RESPONSES.CONJUGATED ANTIBODIES.CONJUGATED ANTIBODIES.NONSPECIFIC ENHANCEMENT OF THE IMMUNE SYSTEM.NONSPECIFIC ENHANCEMENT OF THE IMMUNE SYSTEM